Facile synthesis and physical and spectral characterization of 2,6-di-tert-butyl-4-nitrophenol (DBNP): A potentially powerful uncoupler of oxidative phosphorylation

Journal Article · Tue Jan 31 23:00:00 EST 1995 · Environmental Toxicology and Chemistry; (United States)

DOI:https://doi.org/10.1002/etc.5620140210· OSTI ID:6520187

Rivera-Nevares, J A; Wyman, J F; Minden, D.L. von; Lacy, N; Macys, D A ^[1]; Chabinyc, M L; Fratini, A V ^[2]

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1. Naval Medical Research Inst. Detachment, Wright-Patterson AFB, OH (United States)
2. Univ. of Dayton, OH (United States). Dept. of Chemistry

The compound 2,6-di-tert-butyl-4-nitrophenol (DBNP), a potentially powerful uncoupler of ATP-generating oxidative phosphorylation, has been physically and spectroscopically characterized using X-ray crystallography, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), GC-MS spectrometry, Fourier-transformed IR (FTIR) spectrophotometry, UV-Vis spectrophotometry, and FT [sup 1]H- and [sup 13]C-NMR spectroscopy. However, DBNP is not commercially available; therefore, it had to be synthesized in the laboratory prior to toxicity studies. The DBNP was prepared from 2,6-di-tert-butylphenol (DBP) precursor in hexane through an electrophilic aromatic substitution process using NO[sub 2]. A collective yield of 75% was obtained by using two empirically determined end points that prevented the coprecipitation of reaction by-products and resulted in the formation of DBNP in high purity. Excessive amounts of NO[sub 2] in reaction mixtures resulted in the decomposition of preformed DBNP. With a pK[sub a] value of 6.8 and a higher degree of lipophilicity, DBNP may prove to be a stronger uncoupler of oxidative phosphorylation than 2,4-dinitrophenol due to the expected enhancement of passive-diffusion kinetics across biological membranes at the physiological pH of 7.4. The present study is intended to provide analytical toxicologists, industrial hygiene monitors, and other professionals involved in chemical health and safety with a comprehensive source of basic information on the synthesis and analytical chemistry of DBNP.

• OSTI ID: 6520187
• Journal Information: Environmental Toxicology and Chemistry; (United States), Journal Name: Environmental Toxicology and Chemistry; (United States) Vol. 14:2; ISSN 0730-7268; ISSN ETOCDK
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CHEMICAL ANALYSIS
CHEMICAL PREPARATION
CHROMATOGRAPHY
FOURIER TRANSFORMATION
GAS CHROMATOGRAPHY
INTEGRAL TRANSFORMATIONS
MASS SPECTROSCOPY
NITRO COMPOUNDS
NMR SPECTRA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHYSICAL PROPERTIES
SEPARATION PROCESSES
SPECTRA
SPECTROSCOPY
SYNTHESIS
TOXICITY
TRANSFORMATIONS